To understand what causes immune collapse seen in AIDS, we are investigating the effects of HIV and its envelope on T-cell and macrophage function in vitro. We have observed that HIV has both inhibitory and costimulatory activities on T-cell function when presented simultaneously with reagents which trigger the T-cell receptor. This "costimulatory" activity appears to be most active on naive peripheral T-cells and may explain the immune activation seen in both the CD4 and CD8 subsets of T-cells in HIV infected individuals. We are currently asking whether HIV mediated costimulation can induce abnormal cytokine regulation and contribute to immune dysfunction. In this context, we are studying the effects of virus infection on both T cell and macrophage cytokine production. The results indicate that virus mediates pleiotropic signals that result in either reduced or enhanced cytokine production thereby disrupting the normal balanced function of the immune system leading to AIDS. These studies are important to understanding the immunopathogenesis of HIV and to evaluating the biological effects of AIDS and vaccine therapies targeted at reversing immunological demise.